There is increasing evidence for a genetic contribution to the etiology of certan common cancers. The Utah Mormon population is well-suited to a study of the genetics of cancer because of characteristically large family sizes, migrational stability, and because of the considerable attention members devote to compiling genealogical records. In addition, since this population has a strong commitment to good health, we have enjoyed excellent cooperation in our studies thus far. We will continue to explore our genealogical data base, which now includes 1.2 million individuals, for familial clusters of cancers. Historical cancer cases are documented, and members of cancer-prone families are documented. They are offered genetic counseling in our clinic and asked to give samples for genetic marker assays. Since the establishment of preclinical markers for cancer is of utmost importance in promoting early detection, we are pursuing several new approaches to increase the possibility of finding markers which link to cancer genes. These include new electrophoretic techniques, restriction fragment length polymorphisms, sister chromatid exchange rates, and measurement of polyamine levels in breast fluids. To investigate modes of inheritance, including gene-environment interactions, intensive pedigree analysis is performed on these results. These programs, as well as auxiliary statistical techniques, are undergoing continued refinement and extension. Because of the unique and extensive nature of our data, we are currently developing a new data base management system which can process linked genealogical data conveniently and efficiently. This system, GENISYS, contains a high-level query language which largely frees users from writing computer programs. When completed, GENISYS will greatly enhance our capacity to carry out rapid, large-scale genetic analyses.